Contraction and relaxation of smooth muscle are primary functions of the ionized calcium concentration of the smooth muscle cell. The pools of "activator calcium ion" are unknown in the pulmonary (PVM) smooth muscle. The mechanisms controlling the calcium concentration are also unknown. Prostaglandins, however, appear to be involved in the regulation of PVM tone; the mechanism is unclear. This proposal outlines a series of studies designed to delineate the mechanisms involved in PVM contraction and how these mechanisms differ from peripheral vascular smooth muscle. The hypothesis to be tested is that electrolytes and vasoactive agents change PVM tone by affecting membrane permeability to calcium ion, as well as calcium binding and metabolism. This process is modulated by the smooth muscle prostaglandin system. Utilizing isolated, helical strips of canine pulmonary artery and vein, and mesenteric artery and vein, we will measure 1) tension development in response to prostaglandins, histamine, kinins and electrolytes; 2) extracellular and intracellular content of electrolyte; 3) the efflux and distribution of calcium and prostaglandins associated with the above interventions. These studies should define the mechanisms regulating activator calcium ion in pulmonary muscle. They should also provide insight into the mechanisms which protect the pulmonary vasculature from the functional contractile changes occurring in the peripheral vasculature in pathologic states. This may aid the rationale development and utilization of drugs selectively beneficial in pulmonary vascular disease.